HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Intrahippocampal administration of the branched-chain alpha-hydroxy acids accumulating in maple syrup urine disease compromises rat performance in aversive and non-aversive behavioral tasks.

Abstract
Maple syrup urine disease (MSUD) is an inherited metabolic disease predominantly characterized by neurological dysfunction. Although a variable degree of psychomotor/delay/mental retardation is found in a considerable number of MSUD patients, the mechanisms underlying the neuropathology of this disorder are yet not defined. The present study investigated the effect of acute intrahippocampal administration of the branched-chain alpha-hydroxy acids (BCHA) accumulating in MSUD on rat behavior in non-aversive (open field) and aversive (inhibitory avoidance) tasks. Cannulated 60-day-old male Wistar rats received bilateral intrahippocampal injection of alpha-hydroxyisocaproic acid (HIC, 1.5 micromol), alpha-hydroxyisovaleric acid (HIV, 2.5 micromol), alpha-hydroxy-beta-methyl-n-valeric acid (HMV, 1.5 micromol), or NaCl (2.5 micromol)(controls) immediately after or 10 min before training. Testing session was performed 24 h later. Administration of the hydroxy acids immediately after training caused no effect on the cognitive performance of the rats. In contrast, HIV and HMV administered 10 min before training provoked a habituation deficit in the open field task. Motor activity, assessed by crossing responses, was the same for the groups infused with BCHA and NaCl. The effect of MK-801, succinate, creatine, and the antioxidants ascorbic acid plus alpha-tocopherol on the behavioral alterations provoked by HIV in the open field task revealed that only the energetic substrates (succinate and creatine) prevented these effects, reflecting a possible compromise of brain energy production by HIV. We also observed that rats pretreated with HIC, HIV, or HMV did not increase their latency in the testing session in the step-down inhibitory avoidance task, revealing an impairment of retrieval (memory retention or acquisition) in this task. Furthermore, no differences between controls and rats receiving BCHA were detected in the latency to leave the platform in the training test, suggesting similar motor activity of all groups. The data indicate that the alpha-hydroxy acids accumulating in MSUD impair cognition and may be implicated in the neuropathology and psychomotor delay/mental retardation observed in the affected patients.
AuthorsVilson de Castro Vasques, Fabrício Brinco, Moacir Wajner
JournalJournal of the neurological sciences (J Neurol Sci) Vol. 232 Issue 1-2 Pg. 11-21 (May 15 2005) ISSN: 0022-510X [Print] Netherlands
PMID15850577 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antioxidants
  • Excitatory Amino Acid Antagonists
  • Hydroxy Acids
  • Dizocilpine Maleate
  • Succinic Acid
  • Creatine
Topics
  • Animals
  • Antioxidants (pharmacology)
  • Avoidance Learning (drug effects)
  • Behavior, Animal (drug effects)
  • Creatine (pharmacology)
  • Dizocilpine Maleate (pharmacology)
  • Excitatory Amino Acid Antagonists (pharmacology)
  • Feces (chemistry)
  • Hippocampus (physiology)
  • Hydroxy Acids (administration & dosage, metabolism, pharmacology)
  • Male
  • Maple Syrup Urine Disease (metabolism)
  • Memory (drug effects)
  • Microinjections
  • Motor Activity (drug effects)
  • Rats
  • Rats, Wistar
  • Succinic Acid (pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: